How We Innovate: The T Cell Research Transforming Immunotherapy

As we mark leukemia and lymphoma awareness month, the Rosalind and Morris Goodman Cancer Institute (GCI) is highlighting ongoing research from Principal Investigator Heather Melichar. Her team is investigating T cell-based immunotherapies – revolutionary cancer treatments that have been particularly effective in the fight against pediatric leukemia and lymphoma.

Prof. Melichar’s team studies the fundamental biology of T cells, specialized immune cells with the ability to kill cancer cells, with an eye toward developing or improving current immunotherapies. Understanding how T cells recognize cancer through receptor proteins is a major focus in the Melichar lab, to generate T cell therapies that can target cancer without causing autoimmune attacks on healthy tissues. This work has direct applications in immunotherapies such as engineered T cell receptor (TCR) therapies and cancer vaccines, which require precise knowledge of how T cells distinguish between healthy tissue and cancer cells.

A major challenge to developing new T cell-based therapies is finding the T cell receptors that effectively target cancer cells. Cancer-specific T cells are incredibly rare, and a major bottleneck is the time and cost associated with identifying these cells and sequencing their receptors. To support their efforts, the lab is pursuing innovative projects to develop low-cost, large-scale methods to expedite therapeutic receptor discovery. Leveraging their expertise and interdisciplinary collaborations, they are using advanced live cell microscopy approaches, artificial intelligence, and cutting-edge genome engineering to build high-throughput pipelines that will allow them to link receptor sequences with their targets and identify sequences that effectively discriminate between healthy and cancerous cells. This knowledge is critical to designing safer and more effective immune-based therapies that avoid dangerous off-target effects.

Unfortunately, some pediatric leukemias are unresponsive or develop resistance to current immunotherapies. To address this challenge, the Melichar lab collaborates with molecular oncologists and clinicians to develop models of hard-to-treat leukemias. These pre-clinical models are used by the team to identify molecular vulnerabilities that could present new therapeutic targets. They also serve as a testing ground for new T cell targets born from the lab’s discoveries in T cell biology.

By uniting fundamental T cell research with pre-clinical leukemia models, Prof. Melichar’s team is advancing immune therapies that are both more precise and more effective. As leukemia and lymphoma awareness month reminds us of the challenges posed by pediatric blood cancers, this innovative research offers the potential to transform care.

Heather Melichar | Principal Investigators | Goodman Cancer Institute